Necrotizing enterocolitis (NEC) is a devastating gastrointestinal illness affecting up to 10% of premature infants, with a 30% mortality rate, and formula feeding has been identified as a risk factor for NEC. A study published online on September 8, 2014 in The American Journal of Pathology found that growth factors present in human breast milk, but not in formula, may explain the protection against intestinal damage. Further, supplementing the diet of newborn NEC-affected rodents with these growth factors promotes epithelial cell survival. "NEC is a highly morbid disease that can lead to multiple complications, including intestinal strictures, short gut syndrome, repeated surgeries, and extended hospital stays. Advances in understanding the growth factor signaling cascades that maintain the healthy developing intestine could lead to new methods for treating or preventing this devastating illness," says Mark R. Frey, Ph.D., The Saban Research Institute of Children's Hospital Los Angeles and the Keck School of Medicine of the University of Southern California. Driving this research is the quest to understand how human breast milk protects infants from NEC. Soluble growth factors found in breast milk, such as epidermal growth factor (EGF) and heparin-binding EGF-like growth factor (HB-EGF), are thought to be possible protective molecules. Although both EGF and HB-EGF primarily activate the EGF receptor (EGFR), a member of the ErbB receptor tyrosine kinase family, HB-EGF also activates ErbB4 receptors. "We have recently demonstrated that NRG4, an ErbB4-specific ligand that does not bind or activate other family members, specifically promotes survival but not migration or proliferation of mouse colon epithelial cells," says Dr. Frey. Thus, NRG4 is a potentially unique and selective target for new therapies.
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